Depression is the most common mental disorder that threatens human physical and mental health and has a morbidity of about 5% of the world population. The disease severely affects human health and living quality and is expected to become the second largest disease threatening human health and shortening human life to the year 2020.
The mechanism of antidepressant has not been elucidated up to now. Medicament having obvious treatment effect acts essentially on synapse parts of nerve endings, and plays role by modulating level of neurotransmitter of synapse gaps. Studies on the biochemical of the etiology show that depression is mainly related to five neurotransmitters such as central 5-hydroxytryptamine (5-HT), norepinephrine (NA), dopamine (DA), acetylcholine (Ach) and γ-aminobutyric acid (GABA), etc.
Antidepressants can be classified to two major groups: the early non-selective antidepressants and the novel selective reuptake inhibitors. The non-selective antidepressants include mainly monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs); and selective reuptake inhibitors mainly include (1) selective serotonin (5-HT) reuptake inhibitors (SSRIs) such as fluoxetine and paroxetine, (2) norepinephrine (NA) reuptake inhibitors (NDRIs) such as Reboxitine, (3) norepinephrine-dopamine and specificity 5-HT reuptake inhibitors (NDRIs) such as Mirtazapine, (4) 5-HT and NA reuptake inhibitor (SNRIs) such as Venlafaxine and Duloxetine, and (5) selective serotonin reuptake enhancers (SSREs) such as Tianeptine, etc.
Although a large number of antidepressants are used clinically for treating depression, the treatment is ineffective to many patients and electric convulsive treatment is needed since some medicaments are in low response rate and have possible side effects. Therefore, the development of antidepressants is still the point for the study and research of new medicament and large amount of investment are involved to develop new drugs in many pharmaceutical manufactures.
The current research trends of the development of antidepressant are focused on the following two points: The first is the secondary development of the existing medicaments, including: 1) further developing new indications of the existing medicaments; and 2) changing dosage forms of the existing medicaments.
The second is to further develop new products, which is to develop novel medicaments having better and more prompt effects and safer for treating depression than those commercially available currently by finding compounds that act on new target or multiple targets and have new structural type.
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On the research of new antidepressant, many attentions are focused on the study of the triple reuptake inhibitor currently, which hopefully will solve the problem of delayed effect on the existing antidepressants, and will improve the effectiveness and safety. The triple Reuptake inhibitors, also named as “broad spectrum” antidepressants, refers to compounds that can inhibit the reuptake of three monoamine transporters, i.e. 5-HT. NA and DA that are closely related to depression simultaneously.
The triple reuptake antidepressant is still on the stage of clinical research at the moment. For example, the triple Reuptake inhibitor DOV-216303 developed by DOV Pharmaceutical is on the clinical III-stage, and NS-2359 co-developed by GSK and NeuroSearch is on anti-depression clinical II-stage. These monoamine transporter triple-reuptake antidepressants are advantageous in potent and prompt efficiency, and have become the emphasis in the anti-depression field. The development and research of new antidepressants in China is in the preliminary stage, particularly studies on new antidepressants that acts on three systems: 5-HT, NA and DA, and is an important theme.